P24 HIGH-DOSE CYCLOPHOSPHAMIDE 4 GR/M2 AND STEM-CELL COLLECTION AFTER DARATUMUMAB-BASED QUADRUPLET INDUCTION IN NEWLY DIAGNOSED TRANSPLANT-ELIGIBLE MULTIPLE MYELOMA PATIENTS: A SINGLE-CENTER EXPERIENCE
Authors: C. Liberatore, C. Passeri, F. Fioritoni, O. Iuliani, G. Montanaro, A. Di Nicola, P. Accorsi, S. Santarone, S. Pulini, M. Di Ianni
Journal: HemaSphere (2023)

Background: quadruplet induction with Daratumumab/Bortezomib/Thalidomide/Dexamethasone (Dara-VTd) has become the standard treatment for transplant-eligible newly diagnosed multiple myeloma patients (NDMM). Despite improved response rates, concerns with stem-cell mobilization and collection emerged in CASSIOPEIA trial. Following high-dose cyclophosphamide (HD-CTX) ranging 2 to 3 gr/m2 and granulocyte colony-stimulating factor (G-CSF) 10 μg/kg/day, a greater use of Plerixafor and a lower total number of CD34+cells/Kg collected per patient compared to VTd were reported. Methods: after Dara-VTd induction, NDMM received inpatient HD-CTX 4 gr/m2 followed by G-CSF 5 μg/kg/day starting on day +2 from HD-CTX until last day of collection, as per institutional practice. Plerixafor was administered on demand in patients with <20 CD34+cells/μl on day of planned leukapheresis or in those predicted as poor mobilizer per institutional practice. Main parameters considered on first day of leukapheresis were: patient body weight (kg)/ CD34+cells/μl ratio and peripheral white blood cells/μl/ CD34+cells/μl ratio. Pre-planned total target dose was 10x106 CD34+cells/Kg for multiple autologous stem-cell transplantation (ASCT). Results: from 1st December 2021 to 31st December 2022, 45 NDMM received Dara-VTd at our institution. 23 patients completed induction and were included in this analysis (Figure 1). At diagnosis median age was 62 years (range: 39-70), 17% were ISS III, 13% were R-ISS III and 48% were R2-ISS III-IV. 15 patients (65%) had high-risk cytogenetic abnormalities as del17p13, gain1q21, t(4;14), t(14;16) and t(14;20). After a median of 4 Dara-VTd cycle (range: 4-6) overall response rate was 96%, with 43% VGPR and 35% sCR. 1 patient progressed after 4th cycle. Thalidomide and Bortezomib were reduced in 70% and 17% of patients, respectively. After a median of 135 days (range: 113-190) from start of induction, 22 patients received HD-CTX. No relevant grade 3-4 adverse events were reported. After a median of 11 days (range: 9-13) 22/22 patients underwent leukapheresis; 48% received Plerixafor. Twenty-one patients completed stem-cell collection, harvesting a mean total amount of 10,11 x106 CD34+cells/kg (range: 7,6-14,8) (Table 1). One patient discontinued mobilization due to concomitant Sars-Cov2 infection. Unfortunately both subsequent rescue attempts with chemo-free G-CSF 10 μg/kg/day + Plerixafor and then CTX 2 gr/m2 + G-CSF 10 μg/kg/day + Plerixafor failed. One patient progressed soon after leukapheresis. After a median of 201 days from start of induction (range: 168-283), 15/23 (65%) NDMM patients and 15/21 (71%) of those who completed leukapheresis already underwent ASCT. Mean number of infused CD34+cells was 5,16 x106/kg (range: 3,59-9,86). All patient obtained stable neutrophils and platelets engraftments after a median of 12 days (range: 9-14) and 16 days (range: 13-19), respectively. No relevant toxicities were reported. At last follow up, all patients were alive. Conclusions: after Dara-VTd induction in NDMM, mobilization with HD-CTX 4 gr/m2 and G-CSF 5 μg/kg/day proved feasible and effective in a real-life setting. High incidence of poor mobilizers in Daratumumab-exposed patients was confirmed in our experience. Nonetheless, greater dose of CTX compared to CASSIOPIEA trial together with on-demand and patient-tailored usage of Plerixafor allowed high number of stem-cell collection per patient sufficient for multiple ASCT and favorable transplantation outcomes.